Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Shadow proteins in thymus - Clues to how immune system works?

11.10.2002


Findings could lead to new understanding of diabetes, Crohn’s, and more



Researchers at Joslin Diabetes Center, Harvard Medical School, and other institutions have identified the function of a protein, dubbed aire, that is critical to helping immune cells learn to recognize--and avoid attacking--the far-flung organs and tissues of the body. The protein appears to work by turning on in the thymus, which lies beneath the breast bone, the production of a wide array of proteins from the body’s periphery. The discovery could shed light not only on how the healthy immune system develops tolerance to its own proteins but also how tolerance is lost, as it is in diabetes, rheumatoid arthritis, Crohn’s disease and other autoimmune illnesses.

"Our findings lead back to humans because they tell us about a very important mechanism for controlling autoimmunity," said Diane Mathis, a Harvard Medical School professor of medicine at Joslin. "At the same time, they may help us understand why people develop autoimmune diseases." The findings are reported in the Oct. 11 Science.


Until recently, immune cells, in particular T cells, were thought to learn their most basic lesson--attack foreign proteins but spare those that are native--in one of two places. Those with a broad mandate, namely to monitor widely expressed cellular proteins or proteins circulating in the bloodstream, were thought to be trained to distinguish self from foreign proteins while still in the thymus. Cells that recognize proteins in organs and tissues in the periphery, such as the pancreas, thyroid, and adrenals, were believed to learn the self-vs.-nonself lesson once they left the thymus. This organ was thought incapable of producing proteins made by distant organs such as the liver, brain, and pancreas.

But it appears that T cells in training may be learning the lesson while still in the thymus. Building on work of other groups, first author Mark Anderson, a research fellow in medicine at Joslin; Emily Venanzi, a Harvard Medical School graduate student in immunology; Christophe Benoist, a professor of medicine at Joslin; Mathis, and colleagues, reported that a small network of thymic cells, the medullary epithelial cells, expresses hundreds of genes usually associated with organs such as the pancreas, brain, and liver.

"No one would think you would encounter your big toe protein in the thymus, but in fact proteins from the eye, the liver, from all over the place are specifically expressed in a small population of stromal cells in the thymus," said Benoist.

A majority of these expressed proteins are used by the peripheral organs to tell T cells to stay away. Indeed, the researchers believe the proteins are used in the thymus to foreshadow the very self-antigens that the T cells will encounter once they travel out into the body. "There is a foretelling of these proteins in the thymus, which is why we call it an immunological self-shadow," said Mathis.

In a critical step, the Joslin team discovered that the transcription factor aire plays a critical role in producing these self-shadow proteins in the thymus (hence its name, which is formed from two letters in each word of autoimmune regulator). Mutant mice lacking aire exhibited in their thymus only a fraction of the peripheral self-proteins found in the thymus of normal mice. And the mutants exhibited widespread autoimmunity. In fact, their condition was reminiscent of a condition found in humans carrying a defective AIRE gene, autoimmune polyglandular syndrome.

It is not yet clear how the shadow proteins educate developing T cells inside the thymus, though Benoist suspects the processes are similar to those used to eliminate T cells that react to ubiquitous or circulating proteins. Nor is it clear how aire controls the expression of so many shadow proteins. One possibility is that it works by binding to other transcription factors. "It is going to be interesting to figure out what the mechanism really is," she said.

While novel, the mechanism is probably only one of many that the immune system uses to educate peripheral T cells about the self-vs.-foreign distinction. "It is very dangerous for the immune system to have self-reactive T cells," Anderson said. "It takes advantage of any mechanism to get rid of these cells. So there is a whole net of mechanisms."

Marge Dwyer | EurekAlert!

More articles from Life Sciences:

nachricht Lethal combination: Drug cocktail turns off the juice to cancer cells
12.12.2018 | Universität Basel

nachricht Smelling the forest – not the trees
12.12.2018 | Universität Konstanz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Innovative Infrared heat reduces energy consumption in coating packaging for food

12.12.2018 | Trade Fair News

New Foldable Drone Flies through Narrow Holes in Rescue Missions

12.12.2018 | Information Technology

Obtaining polyester from plant oil

12.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>